crossing96/oncoscreening huggingface dataset:
The current landscape of salvage therapies for patients with bacillus Calmette-Guérin unresponsive nonmuscle invasive bladder cancer.	PURPOSE OF REVIEW: Although radical cystectomy represents the gold standard treatment for patients with high-risk nonmuscle invasive bladder cancer (NMIBC) whose disease does not respond to bacillus Calmette-Guérin (BCG), many patients are unable or unwilling to undergo surgery. The need remains for effective bladder-preserving therapies. This review aims to describe existing treatments, contemporary research in this field and ongoing trials of salvage therapies for patients with BCG-unresponsive NMIBC. RECENT FINDINGS: Intravesical chemotherapy has been utilized frequently in this setting. Emerging data on combination regimens such as intravesical gemcitabine and docetaxel and intravesical cabazitaxel, gemcitabine and cisplatin are promising; nevertheless, larger, prospective trials are needed. Meanwhile, the intravenous checkpoint inhibitor pembrolizumab was recently FDA-approved for patients BCG-unresponsive NMIBC. Encouraging clinical trial results for intravesical nadofaragene firadenovec, oportuzumab monatox and ALT-803 + BCG have been released, while data from trials of other treatment strategies, including novel chemotherapy and drug delivery, augmented BCG immunotherapy, adenoviral and gene therapy, targeted therapy, and combination systemic immunotherapy with intravesical agents, are eagerly awaited. SUMMARY: Several novel salvage therapies offer promise for patients with BCG-unresponsive NMIBC. Patient selection, efficacy, safety, cost and ease of administration must be carefully considered to determine the optimal treatment approach.	bladder
Use of surgical checklist during transurethral resection increases detrusor muscle collection rate and improves recurrence-free survival in patients with non-muscle-invasive bladder cancer.	OBJECTIVE: To elucidate the therapeutic benefits of using a surgical checklist during transurethral resection for non-muscle-invasive bladder cancer. METHODS: A nine-item surgical checklist was established in January 2016 to assess disease risk and resection adequacy, and it was prospectively implemented into clinical practice. Patients diagnosed with non-muscle-invasive bladder cancer who underwent complete resection from January 2009 to August 2019 were included in this study. The presence of detrusor muscle in the transurethral resection specimen and the intravesical recurrence-free survival were compared between patients who underwent transurethral resection before and after surgical checklist implementation. RESULTS: A total of 125 patients who underwent transurethral resection after surgical checklist implementation were reviewed and compared with 125 patients who underwent transurethral resection before surgical checklist implementation. The use of the surgical checklist led to an increase in the proportion of transurethral resection specimens containing detrusor muscle (92% vs 69.6%, P < 0.01) and a decrease in the recurrence rate (19.2% vs 49.6%, P < 0.01). Multivariate analysis showed that transurethral resection without a surgical checklist was an independent predictive factor influencing the absence of detrusor muscle in the transurethral resection specimen (odds ratio 4.78, P < 0.01) and intravesical recurrence (hazard ratio 1.92, 95% confidence interval 1.14-3.23; P = 0.01). Kaplan-Meier plots showed that the recurrence-free survival rate was significantly lower when the surgical checklist was not used (log-rank test result P < 0.01). CONCLUSIONS: This study shows the therapeutic benefits of surgical checklist in improving the quality of resection during transurethral resection and reducing the recurrence rate in patients with non-muscle-invasive bladder cancer.	bladder
Oxidative stress in bladder cancer: an ally or an enemy?	Bladder cancer (BC) is the most common cancer of the urinary tract and despite all innovations, remains a major challenge due to high morbidity and mortality. Genomic and epigenetic analyses allowed the discovery of new genes and pathways involved in the pathogenesis and regulation of BC. However, the effect on mortality has been modest and the development of new targets for BC treatment are needed. Recent evidence suggests that cancer cells are under increased stress associated with oncogenic transformation, with changes in metabolic activity and increased generation of reactive oxygen species (ROS). The increased amounts of ROS in cancer cells are associated with stimulation of cellular proliferation, promotion of mutations and genetic instability, as well as alterations in cellular sensitivity to anticancer agents. Since these mechanisms occur in cancer cells, there is a close link between oxidative stress (OS) and BC with implications in prevention, carcinogenesis, prognosis, and treatment. We address the role of OS as an enemy towards BC development, as well as an ally to fight against BC. This review promises to expand our treatment options for BC with OS-based therapies and launches this approach as an opportunity to improve our ability to select patients most likely to respond to personalized therapy.	bladder
KPNA2 interaction with CBX8 contributes to the development and progression of bladder cancer by mediating the PRDM1/c-FOS pathway.	BACKGROUND: Bladder cancer (BCa) is a common malignancy characterized by high heterogeneity, yet the current treatment modalities are limited. The aim of the present investigation was to unravel the functional role of Karyopherin alpha 2 (KPNA2), a tumor facilitator identified in multiple malignancies, in the progression of BCa. METHODS: BCa tissues and adjacent normal tissues were surgically resected and analyzed from patients with BCa to determine the expression profile of KPNA2 and Chromobox 8 (CBX8) by RT-qPCR, Western blot analysis and immunohistochemistry. The relationship among KPNA2, CBX8 and PR domain zinc finger protein 1 (PRDM1) was explored by co-immunoprecipitation and chromatin-immunoprecipitation. The functions of KPNA2, CBX8 and PRDM1 on BCa cell proliferation, migration and invasion were evaluated. Next, a nude mouse model of BCa was established for validating the roles of KPNA2, CBX8 and PRDM1 in vivo. RESULTS: KPNA2 and CBX8 were highly expressed in BCa and are in association with dismal oncologic outcomes of patients with BCa. KPNA2 promoted nuclear import of CBX8. CBX8 downregulated PRDM1 by recruiting BCOR in the promoter region of PRDM1. Overexpression of KPNA2 promoted the malignant behaviors of BCa cells, which was counteracted by silencing of CBX8. Overexpressing PRDM1 attenuated the progression of BCa by inhibiting c-FOS expression. The tumor-promoting effects of KPNA2 via the PRDM1/c-FOS pathway were also validated in vivo. CONCLUSION: Collectively, our findings attached great importance to the interplay between KPNA2 and CBX8 in BCa in mediating the development and progression of BCa, thus offering a promising candidate target for better BCa patient management.	bladder
Is There a Benefit of Combining Immunotherapy and Radiotherapy in Bladder Cancer?	Immune checkpoint inhibitors have transformed the management of patients with metastatic urothelial cancer, by leading to long-term response and prolongation of survival in a subset of patients. Unfortunately, only one in five patients with metastatic urothelial cancer responds to anti-programmed death ligand-1 ([AQ1]anti-PD-1) monotherapy. Preclinical and early clinical evidence indicates that radiotherapy not only acts locally, but also exerts systemic anti-tumour effects by modulating the immune system. It is hypothesised that combining checkpoint inhibitors with radiotherapy might enhance an anti-tumour immune response and increase response rates. So far, a handful of early phase clinical trials have been performed seeking to answer this question in urothelial cancer patients. The current review summarises the available preclinical and clinical evidence on radiotherapy/immunotherapy combinations in locally advanced and metastatic bladder cancer and suggests future avenues worthy of exploration.	bladder
lncRNA-UCA1 in the diagnosis of bladder cancer: A meta-analysis.	BACKGROUND: The main purpose of this study is to systematically evaluate the diagnostic value of long-chain non-coding RNA urothelial carcinoembryonic antigen 1 (lncRNA-UCA1) for bladder cancer, and to provide a scientific basis for the diagnosis of bladder cancer. METHODS: By searching PubMed, Web of Science, EMBASE, CNKI, Wanfang, Weipu and other databases, in order to collect relevant literature of lncRNA-UCA1 for diagnosis of bladder cancer. The starting and ending time of the search is from the establishment of the database to December 31, 2019. Screen documents and extract data according to inclusion and exclusion criteria. QUADAS entry tool was used to evaluate the quality of literature. Meta-Disc 1.4 and Stata 12.0 software were used for statistical analysis, and UCA1 was combined for the statistics of bladder cancer diagnosis. RESULTS: A total of 7 articles were included in this study, including 954 cases of bladder cancer patients and 482 cases of non-bladder cancer patients. The receiver operating characteristic curve (ROC) curve AUC of lncRNA-UCA1 used to diagnose bladder cancer was 0.86. The sensitivity was 0.83 (95% CI: 0.80-0.85), and the specificity was 0.86 (95% CI: 0.82-0.89). The positive likelihood ratio is 6.38 (95% CI: 3.01-13.55), and the negative likelihood ratio is 0.20 (95% CI: 0.13-0.31). The diagnostic odds ratio is 33.13 (95% CI: 11.16-98.33). CONCLUSION: lncRNA-UCA1 has a high value of clinical auxiliary diagnosis for bladder cancer, and it can be further promoted and applied clinically.	bladder
Bone marrow mesenchymal stem cells-derived exosomal microRNA-19b-1-5p reduces proliferation and raises apoptosis of bladder cancer cells via targeting ABL2.	BACKGROUND: Exosomes are involved in intercellular communication via specialized molecular cargo, such as microRNAs (miRNAs). However, the mechanisms underlying exosomal miR-19b-1-5p in bladder cancer remain largely unknown, thus, we aim to investigate the effect of exosomal miR-19b-1-5p on bladder cancer with the involvement of non-receptor protein tyrosine kinase Arg (ABL2). METHODS: miR-19b-1-5p and ABL2 expression were tested in bladder cancer. miR-19b-1-5p inhibition/elevation assays were conducted to determine its role in bladder cancer. Exosomes were extracted from bone marrow mesenchymal stem cells (BMSCs). Exosomes and T24 cells were co-cultured to verify their function in biological characteristics of bladder cancer cells. RESULTS: miR-19b-1-5p was down-regulated while ABL2 was upregulated in bladder cancer. Exosomal miR-19b-1-5p suppressed malignant behaviors of bladder cancer cells, and also inhibited tumor growth in vivo. Up-regulated ABL2 mitigated the effects of miR-19b-1-5p up-regulation on bladder cancer cells. CONCLUSION: BMSCs-derived exosomal miR-19b-1-5p suppresses bladder cancer growth via decreasing ABL2.	bladder
The Factors Affecting Expansion of Reactive Tumor Infiltrating Lymphocytes (TIL) From Bladder Cancer and Potential Therapeutic Applications.	Tumor infiltrating lymphocytes (TIL) therapy was shown to provide durable objective response in patients with metastatic melanoma. As a fundamental first step to bring TIL therapy to clinical use, identification of patients whose tumors yield optimal numbers of reactive TIL is indispensable. We have previously shown that expansion of tumor reactive TIL from primary bladder tumors and lymph node metastases is feasible. Here, we performed TIL harvesting from additional surgical specimens (additional 31 primary tumors and 10 lymph nodes) to generate a heterogenous cohort of 53 patients with bladder cancer (BC) to evaluate the tumor characteristics that lead to tumor-reactive TIL expansion. Among a total of 53 patients, overall TIL growth from tumor samples were 37/53 (69.8%) and overall anti-tumor reactive TIL were 26/35 (74.3%). Mixed urothelial carcinoma is associated with higher anti-tumor reactivity of expanded TIL than pure urothelial carcinoma (89.5% vs. 56.3%, p=0.049). The anti-tumor reactivity of expanded TIL from primary tumors previously treated with BCG immunotherapy were lower (33.3% vs. 82.6%, p=0.027) although T-cell phenotype (CD3+, CD4+, CD8+, and CD56+) was similar regardless prior of BCG therapy. Addition of agonistic 4-1BB antibody in culture media with IL-2 improved the number of expanded TIL from primary tumors previously treated with BCG immunotherapy. There was no significant difference between basal and luminal subtype tumors in terms of viable and reactive TIL growth. Our study demonstrates that TIL expansion is feasible across all BC patients and BC subtypes, and we suggest that TIL therapy can be a reasonable treatment strategy for various manifestations of BC.	bladder
The effect of body mass index on clinico-pathological features and survival outcome in metastatic bladder carcinoma.	OBJECTIVES: The The study proposed to assess the relation between the body mass index (BMI) and clinicopathological features of metastatic urinary bladder cancer (uBCa) and the influence on survival outcome. METHODS: A retrospective study included 201 metastatic uBCa patients. They classified into three groups according to BMI, group I; a BMI of 18.5-24.9 kg/m2, group II; a BMI of 25-29.9 kg/m2, and group III; BMI ≥ 30 kg/m2. The Kaplan - Meier curve used for survival analysis. RESULTS: 69 patients (34.3%) belonged to group I, 75 patients (37.3%) belonged to group II, and 57 patients (28.4%) belonged to group III. Smoking history was detected in 44.8% of patients with Performance Status (PS) 0 in 55.2%, and PS 1 in 26.9%. Of note, 44.8% of patients responded to 1st chemotherapy and 50.7% received more than 2 lines. Through the univariate analysis, poor prognostic outcome was associated with male (P= 0.01), smoking (P=0.002), BMI group II and group III (p=0.00), PS 2 compared with PS 0 (P&lt;0.001), metastasis to liver, lung, and lymph node (P&lt;0.001), and no response to first line chemotherapy (P&lt;0.001). While no effect for age (P=0.1), bone metastasis (P=0.6), serum LDH (P=0.1), serum albumin (P=0.4), and ≥2 chemotherapy lines (P=0.5) on survival outcome. After the follows-up period, the OS was 12.7 months for all patients. Regarding the BMI groups, the median OS was 23.5 months, 12.9 months, and 10.2 months for group I, group II, and group III respectively (p<0.001). CONCLUSION: High BMI associated with aggressive clinico-pathological features and poor survival outcome in metastatic uBCa.	bladder
Comparison of clinical outcomes in patients with localized or locally advanced urothelial carcinoma treated with neoadjuvant chemotherapy involving gemcitabine-cisplatin and high dose-intensity MVAC.	PURPOSE: To compare the efficacy and safety of high dose-intensity combination of methotrexate, vinblastine, adriamycin and cisplatin (HD MVAC) with gemcitabine plus cisplatin (GC) as a neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) or locally advanced upper tract urothelial cancer (UTUC). PATIENTS AND METHODS: A retrospective analysis was conducted for patients with UC (cT2-4aN0-1M0) who received NAC from January 2011 and December 2017 at Asan Medical Center. Pathologic complete response (pCR), down-staging (< ypT2 and no N upstaging), disease-free survival (DFS), OS and safety were compared for each regimen. RESULTS: Out of a total of 277 patients, 176 patients received GC and 41 patients received HD MVAC. With the exception of age (patients receiving HD MVAC were younger; p = 0.002), other baseline characteristics were well balanced between groups. pCR rates were 27.0% for GC and 22.6% for HD MVAC (p = 0.62), and down-staging rate was 50.8% for GC and 58.1% for HD MVAC (p = 0.47). There were no differences in OS (72.1% vs 73.1% for GC vs HD MVAC; p = 0.58) and DFS (54.9% vs 63.3% for GC vs HD MVAC; p = 0.21) at 3 years. HD MVAC with prophylactic G-CSF was associated with a higher incidence of febrile neutropenia (p < 0.001) than GC. The NAC regimen was not an independent prognostic factor for OS. CONCLUSION: Oncologic outcomes were not significantly different between the GC and HD MVAC when used as NAC in MIBC/UTUC.	bladder
STAG2 as a prognostic biomarker in low-grade non-muscle invasive bladder cancer.	OBJECTIVE: Improvements to bladder cancer risk stratification guidelines are needed to better tailor post-operative surveillance and adjuvant therapy to individual patients. We previously identified STAG2 as a commonly mutated tumor suppressor gene in bladder cancer and an independent predictor of progression in NMIBC. Here we test the value of combining STAG2 immunostaining with other risk stratification biomarkers in NMIBC, and as an individual biomarker in MIBC. MATERIALS AND METHODS: STAG2 immunohistochemistry was performed on a progressor-enriched cohort of tumors from 297 patients with NMIBC, and on tumors from 406 patients with MIBC from Aarhus University Hospital in Denmark. Survival analysis was performed using Kaplan-Meier survival analysis, the log rank test, and Cox proportional hazards models. RESULTS: STAG2-negative low-grade NMIBC tumors were 2.5 times less likely to progress to muscle invasion than STAG2-positive low-grade NMIBC tumors (Log-rank test, P = 0.008). In a composite group of patients with AUA intermediate and high-risk NMIBC tumors, STAG2-negative tumors were less likely to progress (Log-rank test, P = 0.02). In contrast to NMIBC, we show that STAG2 is not useful as a prognostic biomarker in MIBC. CONCLUSIONS: STAG2 immunostaining can be used to subdivide low-grade NMIBC tumors into two groups with substantially different risks of disease progression. Furthermore, STAG2 immunostaining may be useful to enhance NMIBC risk stratification guidelines, though larger cohorts are needed to solidify this conclusion in individual risk groups. STAG2 is not useful as a biomarker in MIBC. Further study of the use of STAG2 immunostaining as a biomarker for predicting the clinical behavior in NMIBC is warranted.	bladder
Non-maintenance intravesical Bacillus Calmette-Guérin induction therapy with eight doses in patients with high- or highest-risk non-muscle invasive bladder cancer: a retrospective non-randomized comparative study.	BACKGROUND: To explore possible solutions to overcome chronic Bacillus Calmette-Guérin (BCG) shortage affecting seriously the management of non-muscle invasive bladder cancer (NMIBC) in Europe and throughout the world, we investigated whether non-maintenance eight-dose induction BCG (iBCG) was comparable to six-dose iBCG plus maintenance BCG (mBCG). METHODS: This observational study evaluated 2669 patients with high- or highest-risk NMIBC who treated with iBCG with or without mBCG during 2000-2019. The patients were classified into five groups according to treatment pattern: 874 (33%) received non-maintenance six-dose iBCG (Group A), 405 (15%) received six-dose iBCG plus mBCG (Group B), 1189 (44%) received non-maintenance seven-/eight-dose iBCG (Group C), 60 (2.2%) received seven-/eight-dose iBCG plus mBCG, and 141 (5.3%) received only ≤5-dose iBCG. Recurrence-free survival (RFS), progression-free survival, and cancer-specific survival were estimated and compared using Kaplan-Meier analysis and the log-rank test, respectively. Propensity score-based one-to-one matching was performed using a multivariable logistic regression model based on covariates to obtain balanced groups. To eliminate possible immortal bias, 6-, 12-, 18-, and 24-month conditional landmark analyses of RFS were performed. RESULTS: RFS comparison confirmed that mBCG yielded significant benefit following six-dose iBCG (Group B) in recurrence risk reduction compared to iBCG alone (groups A and C) before (P < 0.001 and P = 0.0016, respectively) and after propensity score matching (P = 0.001 and P = 0.0074, respectively). Propensity score-matched sequential landmark analyses revealed no significant differences between groups B and C at 12, 18, and 24 months, whereas landmark analyses at 6 and 12 months showed a benefit of mBCG following six-dose iBCG compared to non-maintenance six-dose iBCG (P = 0.0055 and P = 0.032, respectively). There were no significant differences in the risks of progression and cancer-specific death in all comparisons of the matched cohorts. CONCLUSIONS: Although non-maintenance eight-dose iBCG was inferior to six-dose iBCG plus mBCG, the former might be an alternative remedy in the BCG shortage era. To overcome this challenge, further investigation is warranted to confirm the real clinical value of non-maintenance eight-dose iBCG.	bladder
Profiling of CYP4Z1 and CYP1B1 expression in bladder cancers.	Bladder cancer is the tenth most common cancer worldwide, where its burden remains a challenge and needs new novel therapies. Several reports indicate expression of CYP4Z1 and CYP1B1 in many tumours. Their expressions are associated with a poor prognosis, and therefore proposed as promising biomarkers or targets for anticancer therapy. By using immunohistochemistry, expression of CYP4Z1 and CYP1B1 was evaluated in a panel of different types of bladder cancer, and the enzymes' relation to histopathological features were assessed. Results showed an increased expression of CYP4Z1 (54.3%) and CYP1B1 (76.9%) in the majority of bladder cancers compared to weak or lack of expression of both enzymes in normal tissues. CYP4Z1expression was significantly associated with tumour grade and stage where the expression was markedly increased in a high grade and advanced stage of the disease (p < 0.05). Additionally, CYP1B1 expression was also associated with TNM staging (p < 0.05) and its expression was increased in patients with lymph node metastasis. The expression profiles of CYP4Z1 and CYP1B1 suggest that both enzymes have the potential to be biomarkers or targets for novel anticancer therapy for bladder cancer. Nevertheless, further studies are needed to better delineate whether these enzymes are druggable targets.	bladder
In vitro and in silico assessment of the effect of WWOX expression on invasiveness pathways associated with AP-2 transcription factors in bladder cancer.	BACKGROUND: WW Domain Containing Oxidoreductase (WWOX) belongs to the unusual tumor suppressors, whose molecular function is not fully understood in bladder cancer, especially regarding interaction with Activator Protein 2 (AP-2) α/γ transcription factors. Thus, using lentiviral systems we created an in vitro model overexpressing or downregulating WWOX in CAL-29 cell line to assess invasiveness pathways. Surprisingly, while WWOX overexpression was accompanied with increased expression of both AP-2 factors, its downregulation only affected AP-2α level but not AP-2γ which remained high. METHODS: Using cellular models and unpaired t-test or Wilcoxon test, we investigated significant changes in biological processes: clonogenicity, extracellular matrix adhesion, metalloproteinases activity, 3D culture growth, proliferation, mitochondrial redox potential and invasiveness. Relative gene expression acquired through Real-Time qPCR has been analyzed by Welch's t-test. Additionally, using oncoprint analysis we distinguished groups for bioinformatics analyzes in order to perform a follow-up of in vitro experiments. RESULTS: Downregulation of WWOX in bladder cancer cell line intensified ability of single cell to grow into colony, mitochondrial redox potential and proliferation rate. Moreover, these cells shown elevated pro-MMP-2/9 activity but reduced adhesion to collagen I or laminin I, as well as distinct 3D culture growth. Through global in silico profiling we determined that WWOX alters disease-free survival of bladder cancer patients and modulates vital processes through AP-2 downstream effectors. CONCLUSIONS: Our research indicates that WWOX possesses tumor suppressor properties in bladder cancer but consecutive examination is required to entirely understand the contribution of AP-2γ or AP-2α.	bladder